Feed compositions containing paraamino-methyl-benzene-sulfonamide and method of using same



United States Patent 3,192,107 FEED COMPOSITIONS CONTAINING PARA-AMINO-METHYL-BENZENE-SULFONAMIDE AND METHOD OF USING SAME ClarenceWalter. Whitmoyer, James Ross Wiley, and Timothy Scott Chang, Myerstown,Pa., assignors, by mesne assignments, to Whitmoyer Laboratories, Inc., acorporation of Delaware No Drawing. Filed Nov. 29, 1962, Ser. No.241,030 Claims priority, application Great Britain, Dec. 12, 1961,44,394/ 61 12 Claims. (Cl. 167 53) This invention relates generally tofeeding stuffs for animals and poultry, more specifically livestock suchas pigs, chickens and turkeys; the invention relating more particularlyto new feed composition containing a chemical compound having favorablegrowth-promoting characteristics andto a method of stimulating andaccelerating the growth of such animals by administration of thechemical compound together with a basal diet which is nutritionallyadequate per se for normal growth.

According to the present invention there is provided a feed compositionwhich contains, as a growth-promoting agent, a compound having as itsactiveingredient para-amino-methyl-benzene-sulfonamide (which may alsobe named p-sulphamoyl-benzylamine). It has been found that when thiscompound is administered to animals as an additive to a basal ration orfeed at certain levels within limited ranges of concentration that theirgrowth will be stimulated and materially accelerated. It will beunderstood that the term animals as herein used is intended tomean suchordinary farmyard animals aspigs, chickens, turkeys and the like. Thecompound, which is herein referred to an additive, may be administeredto the animals by incorporating it in the nutritionally adequate basalrations which, for present purposes, will be understood to be solid feedsuch as feed mash, grain mixtures, or other comminuted mixturesconstituting basal feedstulfs, including also liquidfeedstuff or, thecompound ,may be incorporated in drinking water supplied to thelivestock along with the solid feed.

The use of para-amino-methyl-benzene-sulfonamide and its salts as anadditive to the basal dietis-particularly advantageous in the nutritionofpigs, chickens and turkeys, since they show material weight gains andincreased efficiency of feed utilization when their normal basal dietsare supplemented with a comparatively small percentage of thisgrowth-promoting compound, it having been found that the incorporationof the compound in the feed'in ,a concentration within the range of0.005%

or other unwanted or undesirable side effects.

In practicing the invention, we prefer to useparaamino-methyl-benZene-sulfonamide in the form of the hydrochloridesalt and to incorporate this in effective concentration in a solid feed,although other salts of para-amino-methyl-benzene-sulfonamide and thebase itself have also been found to be effective in accelerating growth.The feed composition may be based on any conventional feed compounded inaccordance with established principles for basal adequate diet for theparticuilar animal or bird to which it is to be fed. The activeingredient is added to the feed in amounts within the limited range setforth above and may be administered tothe animals by placing the feedbefore the animals to be available at all times for consumption adlibitum or it may be administered by controlled interrupted feeding,taking into account that the animal should not partake of more than theproportionate amount in its daily diet than is desirable for effectiveresults. It is preferred to incorporate the active ingredient in anamount of about 0.025% when incorporated in solid feed since this leads3,192,107 Patented June 29, 1965 ice to economy in the use of the activeingredient and ordinarily the results obtained are not significantlypoorer than can be obtained when larger quantities of the additive areincorporated in the feed composition. Although in certain'instanceslarger amounts in the diet than neces-, sary for satisfactory growthpromotion may be added without toxic effect, it will be understood thatthe amount of additive preferably to be incorporated in' the diet willbe largely governed by'the rules of economy. In some instances it isfound that somewhat better results may be obtained by incorporating aquantity of compatible vitamin preparation in the feed composition inaddition to the active growth-promoting ingredient above referred to.Addition of the vitamin preparation is preferably made in the range ofabout 0.2% to 0.5%. Such vitamin prep aration may be a multivitaminpreparation of the type known and conventionally employed in animalfeeding stuffs.

To illustrate the effects of para-amino-methyl-benzenesulfonamide andthe salts thereof as an active ingredient in animal feed rations forstimulating and increasing or accelerating growth there are describedhereinafter various illustrative experiments or tests.

In one experiment the active ingredient in the form of the hydrochloridesalt (para-amino-methyl-benzenesulfonamide-hydrochloride) was tested atthree levels, i.e., 0.1%, 0.05% and 0.025% ofthe basal diet fed tochicks, with a simultaneous, negative control group; that is, the dietof the control group did not contain any additive. The basal diet was aproprietary chick mash excluding any growth-promoting additives.

Two groups of ten male and ten female New Hampshire Rex X Light Sussex,day-old chicks were allocated at random to each of the treatments.Initial live weights were recorded initially and at 1, 2, 3, 4, 6, 8 and10 /2 weeks of age. Group feed consumption was recorded throughout.

i The birds were housed in experimental broiler pens on wood shavingsand were brooded under infra-red lamps. Food and water was supplied adlibitum.

The average weight gains for each group are set out in Tables I and II.A summary of these tables is as follows: I Table I Percentage Averageweight gain (grams) Group active ingredient 1 1 wk. 2 wks. 3 wks. 4 wks.

A 0. 1 28. 5 86. 8 182. 1 289. 6 B 0. 05 29. 9 87. 2 181. 0 291. 4 C 0.025 27. l 82. 1 176. 6 283. 4 D (Control) 24. 7 77. 6 161. 2 256. 3

, Para-amino-methyl-benzene-sullonamide-hydroehloride.

Table 11 Percentage Average weight gain (grams) Group active ingredient1 6 wks. 8 wks. 10% wks.

0. 1 558. 6 1, 015.6 1, 412. 1 0.05 545. 7 976. 7 1, 412. 1 C- 0.025539. 4 985. 3 1, 446. 9 I) (Control) 531. 6 938. 1 1, 325 8 1 Para-aminomethyl-benzenefsulfonamide'hydrochlorlde.

The tabulated results show that the active ingredient has provided asignificant growth increase at all three levels of administration. The0.025% level appears almost as beneficial as the higher levels, therebeing little consistent difference between the three treatments.

It was also found that there wasan improvement in feed conversion as aresult of the dietary additions.

In the following tables there are set forth in tabular form the resultsof other tests which were carried out with pigs, chickens, :and turkeyswith different salts of paraamino-methyl-benzene-sulfonamide and thebase itself. In the following tables certain abbreviations are used forconvenience. The abbreviation for the base(para-aminornet-hyl-benzene-sulfonamide) is PAMBS. Salts of this baseare indicated by adding the name or abbreviation of the name of thesalt, hence-PAMBS HCl-indicates the hydrochloride salt(para-amino-methyl-benzene-sulfonamide-hydrochloride) In Tables III to Vthere are shown tests conducted with chickens, the additive compoundedin the feed, the number of birds in the groups, average weight gain atparticular ages, feed consumption per bird, and feed efficiency. It willbe understood that the controls were fed only the basal ration without:any additive... Feed efiiciency refers to amount of feed consumed perunit Weight gain; for example, pounds of feed per pound of weight gain.The feed in each test was a nutritionally adequate feed per se fornormal growth.

Table III OHICKENS (DAY-OLD CHICKS) Average Feed con- Group No. ofweight at sumption Feed birds 4-wk.-old (11).) efficiency 1. PAMBS 1101,0.05%.. 25 516 1.80 1.73 2. PAMBS H01, 0.025%-. 25 514 1. 84 1. 77 3.PAMBS E01, 0.01% 25 513 1. S8 1. 82 4. PAMBS H01, 0.05% 25 527 1. 921.80 .5. Vitamins 25 509 1.86 1.81 6. Avita* 25 490 1.83 1.86 7. Control25 471 1. 78 1. 88

8. PAMBS H01, 005% and vitamins 25 523 1. 83 1. 73 9. PAMBS H01, 0.025%

and vitamins 25 542 1. 91 1. 74 10. PAMBS'HC], 0.01% and *Avita: Aproprietary antibiotic composition (0.4 lb.ltn) and Vitamins (2gms./lb.).

Percent: PAMBS H01 content in the feed.

Vitamin level: 2 grams per pound of feed. It will be observed from theresults of the tests as set forth in Table III thatpara-amino-rmethyl-benzene-sulfonamidehydrochloride is efi'ective as agrowth promoter and accelerates weight gain, increases feed consumptionand feed efiiciency.

There is shown in Table IV another series of tests with chickens.

Table IV GHICKENS Average Feed con- Group No. of weight at sumption Feedbirds 4-Wk.-0ld (1b.) efficiency 15. PAMBS H01, 0.1% and vitamins 25556 1. 95 1. 73 16. PAMBS H01,

vitamins 25 555 1. 99 1. 76 17. PAMBS 1101, 0.025%

and vitamins 25 550 1. 95 1. 18. PAMBS H01, 0.01% and 21. PAMBS H01,0.1% and vitamins 25 538 1. 1. 79 22. PAMBS H01, 0.05% and vitamins 25574 2.05 1.75 23; PAMBS H01, 0.025%

and vitamins 25 548 1. 99 1. 79 24. PAMBS H01, 0.01% and The chickens inthe. tests referred to in Table IV were grown from 0 to 4 weeks of age,in batteries. Then they were transferred to floor pens covered withlitter. Test groups fed PAMBS HCl at 0.05% level plus vitamins It willbe noted from the above tests that average weight of groups 16 and 22was 13-|% over the control group at 6 weeks old. It was 7% better thancontrol group at eight weeks old. Feed consumption and feed efiiciencywere better in PAMBS HCl groups as compared to the control group.

The tests summarized in Table V Were'conducted with chickens on litterpens from day-old to 7-Week-old with a known coccidiostat in the sameamount in the feed of each group. Infra-red electric brooders were used.Paraamino-methyl-benzene-sulfonamide-hydrochloride was incorporated asan additive to the feed as shown in the table.

Table V CHIOKENS Average Average Feed con- Group No. of weight at weightat sumption Feed efbirds 4-wk.-o1d 8-wk.-0ld (1b.) ficiency Control 6081, 205 6. 28 2. 45 PAMBS H01 0.025% 125 545 1, 274 6. 30 2. 32 PAMBS E01Control 125' 509 1, 6. 17 2. 51 PAMBS H01 0.025% 125 548 1, 257 6. 34 2.37 PAMBS H01 Basal ration used in these tests contained protein 21.58%,fat 3.42% and fiber 3.56% and also=a coccidiostat. The results showedthat groups which included the additive PAMBS I-ICl had 7% better weightgain than the control groups and also had better 'feed consumption andbetter feed efiiciency as compared to the control groups.

The. following Table VIA shows the results of tests with turkeys. Thetests were conducted in litter pens from day-old to four weeks old.. Acommercial turkey starter ration was used as the basal diet.

Table VIA TURKE YS Average Average Feed con- Group No. of weight atweight at sumption Feed efbirds 4-Wk.-old 8-wk.-old (1b.) ficiencyControl 50 223 642 2. 27 1. 77 PAMBS H01 0.025 50 244 714 2. 34 1. 62PAMBS H I 0.0125%- 50 242 698 2. 32 1. 65

Control 50 238 682 2. 32 l. 69 PAMBS 1101 0.025% 50 243 724 2. 35 1. G1PAMBS H01 The results show that the PAMBS HCl treated groups had betterweight gains and better feed efliciency at four weeks of age thanthecontrol groups (9% for 0.025% and 7% for 0.0125 of PAMBS HCl).

Table VI-B shows the results of tests with 300 Broad Breasted Bronzeturkeys divided into three test groups of 100 each. The turkey poultswere raised in a brooder house for four weeks and then transferred topole shed until 16 weeks old. All were raised under like conditionsexcept taht the control group received no PAMBS HCl in their feed; thefeed of the other two groups contained PAMBS HCl throughout the 16 weekperiod as indicated in Table VI-B.

6 In thefollowing tests with chickens (Tables VIII and IX) the amount ofadditive in each case was at a level which is the equivalent of 0.025%of the base (paraamino-rnethyl-benzene-sulfonamide) in the feed. Thecontrol was the same basal ration as those which contained the additive,but of course, it contained no additive. All groups were otherwisetreated under the same conditions in the respective tests.

Table Vl-B TURKEYS 4-wk.-0ld 8-wk.-old 12-wk.-old 16-wk.-old

Group No. birds Av. wt. Feedefii. Av.wt. Feedetfi. Av. wt. Feedefii. Av.wt. Feedefli.

01 100 576 1. 92 4. 95 1. 96 9. 88 2.47 16.21 2.82 PAMBS H01 0.0125 100641 1.72 5. 20 1.94 10.69 2. 34 16. 66 2.75 PAMBS H01 It will be seenthat the turkey groups which received Table VIII the PAMBS HCl showedbetter weight gain and feed ef- CHIOKENS ficiency than the controlsthroughout the test.

The results of tests with pigs conducted under ordinary Average Feed andnatural farm conditions are shown in Tables VII-A Group No.01 weightconsump- Feed and VII-B. The pigs wereconfined 1n separate pens blrds $25 5 eficiency under similar conditions. The tests tabulated in TableVII-A were started when the pigs were 8 weeks of age' PAMBS Aoetate 25580 2.06 1.74 and terminated 29 days later. 2% %r m 25 223 207 B enzoae. 25 2.06 1. As shown in the above table there was a better weight 35PAMBS Carbarsone 25 673 207 L77 gain (4.1%) for the PAMBS HCl group ascompared to PAMBS Formate 25 589 ,7 controls. There was a significantimprovement in feed Control 25 556 77 efficiency (6.1%) for the PAMBSHClgroup.

Table VII-A PIGS Average Average Average Average No. of pigs initialfinal daily at y Feed weight 1 weight gain feed mtake efiiciency (1b.)(1b.) (1b.) b.)

column.-- 14 37. 1 208. 9 1. 47 5. 08 s. 46 Flaws; H01

' 5 in feed"? 14 34.9 213.2 1. 53 4.98 3.25

Table VII-B PIGS Average Average Average Average No. of pigs initialfinal daily daily Feed weight weight gain teed mtake eflicieney (1b.)(1b.) (1b.) (1b.)

Control '16 23.1 36.0 .45 1.63 3.65 Pails/g3; H01

. 5 in reed"? 16 24.4 43.4 .66 1. 94 2.95

There were highly significant increases in daily weight... Table IX gain(47.3%) and feed efficiency (19.2%) for the' CHICKENS PAMBS HCl groupover the controls.

Average Feed In the forego ng tests 1t s shown that thehydrochlorldeGroup N9. of weight copsump Fleed salt ofpara-amino-methyl-benzene-sulfonamide base and bll S af izgfia 1 1(rlagr) efiicieney also the acid addition salts thereof are effective asadditives to the basal animal ration for promoting and ac- '1 2%52ghenyLsuccmatmu 25V 559 ropionate 25 588 .11 celerating growth. Resultsof tests with other salts and PAMBS silicylateun 25 565 2.02 1.75 thebase compared with controls to which no additlve lzih agg slglphiiten 251 3.84 I were included are set forth in the following Tables VIIIOontroLiffiIII -I 25 538 2:06 1:89

and IX.

In the following Table X there are shown the results in the drinkingwater. The chicks beginning at day-old 8 treatments for C.R.D. which areaimed only at one causative organism often are of little help.

It has been found that if para-amino-methyl-benzenesulfonamide compoundsare incorporated in the feed rato four weeks of age were fed a basalration without any tion for poultry so that the active part of thecompound, additives. In two groups the hydrochloride salt as innamely,the base part, para-amino-methyl-benzene-suldicated was added to thedrinking water. In the control fonamide is present within the range of0.05 to 0.5%, in group the drinking water did not contain any additive.solid feed or in the drinking water that the additive has The tests showthat chickens to which the additive was a very favorable effect intreating naturally occurring administered by including it in theirdrinking water showed 10 C.R.D. complex. A number of tests have beenconbetter weight gain, feed consumption and feed efficiency ducted withchickens obtained from commercial broiler than the control group.producers where diagnostic examination showed that the chickens wereinfected by C.R.D. complex. For pur- Table X poses of the tests todetermine the effectiveness of the GHICKENS compound in treating C.R.D.a large number of chickens from a common source was divided at randominto Average Feed groups of eight each. Each group was. fed ad libitumGroup gf g $25 1! QQZ QE' QESS a commercial feed nutritionally adequatefor normal old (gm) bird (1b.) growth and there was incorporated in thefeed for the different groups anamount of para-amino-methyl-ben- Control652 2.11 1-88 zene-sulfonamide-hydrochloride (the active ingredient), figfi gjqfjffffff?i 25 591 2.18 1. 80 as shown in the following tables,with results as tabulated PAMBS Hydrochloride, therein. The criteriaused to judge the efficacy of the 25 575 chemical compound were weightgains at the end of the 25 test, feed consumption, feed efficiency andtracheal swab PAMBS HCl was used in the water at 0.00625 and bacterialcount for organisms found in C.R.D. infected 0.0l25% levels continuouslythroughout the test eXCept chickens. Results were tabulated at the endof one 1116 COHtIOlSw vcl'lflilvifills receiving PAMBS Hcl in the weekand at the end of two Weeks after beginning the water showed betterweight gain, feed consumption and treatment. Comparison was made with acontrol group feed efiiciency than the control group. Inasmuch as whichwas fed in the same manner but without the inchickens ordinarily partakeof about twice as much water corporation of the active ingredient. asfeed by Weight, the concentration of the additive in The followingTables XI and XII show the results of the drinking water is preferablyreduced propontionately. tests conducted with broiler chickens whichwere at the It has also been discovered that the feed composition age atthe beginning of the test as shown in the respective provided by thisinvention is effective not only to acce1etables.

Table XI CHIOKENS 7 WEEKS oLD Feed Tracheal bact. No. of Weight eon-Feed count Group birds gain snmpeth- (percent) tion ciency (1b.) l-wk.2-wk.

PAMBS Ho10.2% Water- 8 58 3.16 2. 39 95,810 73,246 PAMBS HC10.5% Feed. 853 3.17 2.62 67,205 102,081 Control 8 52 3.21 2.72 103, 043 147, 509

PAMBS 21010.27, Water- 8 52 2.96 2. 49 100,909 53. 521 PAMBS HC10.5%Feed 8 50 2.75 2. 43 118, 491 103,157 Control 8 48 3.14 2.88 150,985154, 776

Table XII CHICKENS 6 WEEKS OLD Feed Tracheal baet. No. of Weight cou-Feed count Group birds gain sumpeni- (percent) tion clency (1b.) l-wk.2-wk.

PAMBS E01 0.25% Feed- 8 91 3. 89 2. 39 70, 059 3,910 Control 8 69 3.622.90 68,288 52,166

rate growth when fed to poultry but it is also effective in treatingchronic respiratory disease, often commonly referred to'as C.R.D., orperhaps more aptly, C.R.D. complex. The cause of C.R.D. complex as itoccurs in the field is not clearly defined. Many factors play a part.Mycoplasma gallisepticum, virus infections such as Newcastle disease andinfectious bronchitis, E. coli and other organisms are a part of thecause.

The following Table XIII shows a summary of results of'a large number oftests conducted with'chickens. The table istbased upon averages in eachcase of the number of tests shown in the column entitled N0. of Tests.It should be noted that the figures in this column indicate the numberof tests and not the number of chickens in the test. The number ofchickens in each group in each Therefore test is seven or more.

Table XIII SUMMARY TESTS WITH CHIOKENS Av. Tracheal Group N o. of weightFeed bact. count tests gain efficiency at 2-w1r. after (percent)treatment PAMBS HCl 0.5% Feed. 4 57 2. 60 44, 291 Control 4 52 2. 92 69,042

PAMB S H010.25% Feed 7 56 2. 54 47, 200 Control 7 48 2. Q 97, 061

PAMBS HCl 0.1% Feed. 7 60 2. 69 122, 834 Control 7 51 2. 90 139, 411

PAMBS E01 0.05% Feed. 2 65 2. 46 193, 984 Control 2 59 2. 72 275, 544

PAMBS H01 0.2%

Water 3 58 2. 71 35, 436 Control 3 67 2. 84 78, 514

PAMBS H01 0.1%

Water 2 66 2. 71 80, 094 Control 2 56 3. 02 121, 616

PAMBS H01 0.075%

Water 2 68 2. 41 170, 408 Control 2 59 2. 72 275, 544

It will be observed from the foregoing thatpara-aminomethyl-benzene-sulfonamide and its salts are effective as anadditive to the normal diet of animals in obtaining accelerated growthor weight gain, better feed consumption, better feed efliciency andlower bacterial count with respect to C.R.D. in poultry than is obtainedby the normal diet without such additive.

The terms and expressions which have been employed herein are used asterms of description and not of limitation, and there is no intention,in the use of such terms and expressions, of excluding any equivalentsof the features shown and described or portions thereof, but it isrecognized that various modifications are possible within the scope ofthe invention claimed.

What is claimed is:

1. A feed composition for promoting the growth of swine which comprisesa mixture of a feed nutritionally adequate per se for normal growth ofthe swine and 0.005% to 0.5% of a compound selected from the classconsisting of para-amino methyl benzene sulfonamide and the saltsthereof.

2. A feed composition according to claim 1 in which the mixture containsabout 0.025% of the compound selected from the class consisting ofpara-amino-methylbenzene-sulfonamide and the salts thereof.

3. A feed composition for promoting the growth of poultry whichcomprises a mixture of a feed nutritionally adequate per se for normalgrowth of the poultry and 0.005% to 0.5% of a compound selected from theclass mnsisting of para-amino methyl benzene sulfonamide and the saltsthereof.

4. A feed composition according to claim 3 in which the mixture containsabout 0.025% of the compound selected from the class consisting ofpara-amino-methylbenzene-sulfonamide and the salts thereof.

5. A method of accelerating growth of swine which 10 comprises feedingthe swine ad libitum rations supplying an eifective out non-toxic amountfor growth promotion of a compound selected from the class consisting ofparaamino-methyl-benzene-sulfonamide and the salts thereof.

6. A method of accelerating growth of swine which comprises feeding tothe swine ad libitum a mixture of feedstuff nutritionally adequate perse for normal growth of the animals and 0.001% to 0.5 of a compoundselected from the class consisting ofpara-amino-methylbenzene-sulfonarnide and the salts thereof.

'7. A method according to claim 6 in which the mixture contains about0.025% of the compound selected from the class consisting ofpara-amino-methyl-benzene-sulfonamide and the salts thereof.

8. A method of accelerating growth of poultry which comprises feedingthe poultry ad libitum rations supplying an effective but non-toxicamount for growth promotion of a compound selected from the classconsisting of para-aminc-*nethyl-benzene-sulfonamide and the saltsthereof.

9. A method of accelerating growth of poultry which comprises feeding tothe poultry ad libitum a mixture of feedstuif nutritionally adequate perse for normal growth of the animals and 0.001% to 0.5% of a compoundselected from the class consisting ofpara-amino-methylbenzene-sulfonamide and the salts thereof.

10. A method according to claim 9 in which the mixture contains about0.025% of the compound selected from the class consisting ofpara-amino-methyl-benzenesalts thereof sufiicient to provide adequatenon-toxic dosage to effectively attack the organisms in the bodies ofsaid birds which are the causitive agents of said disease together witha feed ration nutritionally adequate per se for normal growth of saidbirds.

12. A method of accelerating growth and simultaneously treating poultryinfected with the organisms which cause the disease known as C.R.D.complex which comprises feeding ad libitum to the infected birds afeedcomposition comprising a mixture of poultry feed adequate per se fornormal growth of the poultry and 0.001% to 0.5 of a compound selectedfrom the class consisting of para-amino-methyl-benzene-sulfonamide andthe salts thereof.

References Cited by the Examiner Hawking, The Sulphon-amides, 1950,Lewis and Co., London, England, pages 128, 129, 304 and 305.

U.S. Dispensatory25th edition, 1955, Lippincott Co., Philadelphia, Pa,pages 1990 and 1991.

JULIAN S. LEVlTT, Primary Examiner.

FRANK CACCIAPAGLIA, In, LEWIS GOTTS,

Examiners.

1. A FEED COMPOSITION FOR PROMOTING THE GROWTH OF SWING WHICH COMPRISESA MIXTURE OF A FEED NUTRITIONALLY ADEQUATE PER SE FOR NORMAL GROWTH OFTHE SWINE AND 0.005% TO 0.5% OF A COMPOUND SELECTED FROM THE CLASSCONSISTING OF PARA-AMINO-METHYL-BENZENE-SULFONAMIDE AND THE SALTSTHEREOF.